Preliminary Evidence of the in Vitro Effects of BDE-47 On Innate Immune Responses in Children with Autism Spectrum Disorders

Background: Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that manifest in childhood. Immune dysregulation and autoimmune reactivity may contribute to the etiology of ASD and are likely the result of both genetic and environmental susceptibilities. Objectives: We examined a common persistent organic pollutant, 2,2',4,4'-tetrabrominated biphenyl (BDE-47), for differential effects on the immune response of peripheral blood mononuclear cells (PBMC) isolated from children with ASD (n=19) and age-matched typically developing controls (TD, n=18). Methods: PBMC were exposed in vitro to either 100 nM or 500 nM BDE-47, before challenge with an innate immune activator bacterial lipopolysaccharide (LPS), or the T cell mitogen phytohemagglutin A (PHA). Resultant cytokine production was then measured using the LuminexTM multiplex platform. Results: The cytokine responses of LPS stimulated PBMC from ASD and TD subjects diverged in the presence of 100 nM BDE. For example, cells cultured from the TD group demonstrated significantly decreased levels of the cytokines IL-12p40, GM-CSF, IL-6, TNFα, and the chemokines MIP-1α and MIP-1β following LPS stimulation of PBMC pretreated with 100 nM BDE-47 compared with samples treated with vehicle control (p<0.05). In contrast, cells cultured from subjects with ASD demonstrated an increased IL-1β response to LPS (p=0.033) when pretreated with 100 nM BDE-47 compared with vehicle control. Pre-incubation with 500 nM BDE-47 significantly increased the stimulated release of the inflammatory chemokine IL-8 (p<0.04) in cells cultured from subjects with ASD but not in cells from TD controls. The T cell cytokine response following PHA stimulation was also differentially affected in the ASD subjects. There was an increase in the inflammatory cytokine IL-12p40 production in the ASD samples following exposure to 100 nM PBDE-47 compared to a reduction in the TD controls (p=0.007). Conclusions: These data suggest that in vitro exposure of PBMC to BDE-47 affects cell cytokine production in a pediatric population. Moreover, PBMC from the ASD subjects were differentially affected when compared with the TD controls suggesting a biological basis for altered sensitivity to BDE-47 in the ASD population.